Lab-scale flow chemistry? Just do it yourself!

Vázquez-Amaya, Laura Y.; Coppola, Guglielmo A.; Van der Eycken, Erik V.; Sharma, Upendra K.

doi:10.1007/s41981-024-00312-5

Cited by 3 publications

(1 citation statement)

References 153 publications

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“…While several commercial solutions offer perspectives on seamless scalability, their cost remains a significant barrier. DIY lab-scale flow setups, on the other hand, offer low-tech, low-cost solutions that are broadly adoptable . Affordable and widely available polymer or metal tubings (usually with a 1/16” outer diameter) and parts can be diverted to construct lab-scale prototypes able to explore the vast landscape of SH conditions.…”

Section: At Which Cost? Reactors Suitable For Superheated Flow Chemistrymentioning

confidence: 99%

New Opportunities for Organic Synthesis with Superheated Flow Chemistry

Bianchi,

Monbaliu

2024

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Flow chemistry has brought a fresh breeze with great promises for chemical manufacturing, yet critical deterrents persist. To remain economically viable at production scales, flow processes demand quick reactions, which are actually not that common. Superheated flow technology stands out as a promising alternative poised to confront modern chemistry challenges. While continuous micro-and mesofluidic reactors offer uniform heating and rapid cooling across different scales, operating above solvent boiling points (i.e., operating under superheated conditions) significantly enhances reaction rates. Despite the energy costs associated with high temperatures, superheated flow chemistry aligns with sustainability goals by improving productivity (process intensification), offering solvent flexibility, and enhancing safety. However, navigating the unconventional chemical space of superheated flow chemistry can be cumbersome, particularly for neophytes. Expanding the temperature/pressure process window beyond the conventional boiling point under the atmospheric pressure limit vastly increases the optimization space. When associated with conventional trial-and-error approaches, this can become exceedingly wasteful, resource-intensive, and discouraging. Over the years, flow chemists have developed various tools to mitigate these challenges, with an increased reliance on statistical models, artificial intelligence, and experimental (kinetics, preliminary test reactions under microwave irradiation) or theoretical (quantum mechanics) a priori knowledge. Yet, the rationale for using superheated conditions has been slow to emerge, despite the growing emphasis on predictive methodologies. To fill this gap, this Account provides a concise yet comprehensive overview of superheated flow chemistry. Key concepts are illustrated with examples from our laboratory's research, as well as other relevant examples from the literature. These examples have been thoroughly studied to answer the main questions Why? At what cost? How? For what? The answers we provide will encourage educated and widespread adoption. The discussion begins with a demonstration of the various advantages arising from superheated flow chemistry. Different reactor alternatives suitable for high temperatures and pressures are then presented. Next, a clear workflow toward strategic adoption of superheated conditions is resorted either using Design of Experiments (DoE), microwave test chemistry, kinetics data, or Quantum Mechanics (QM). We provide rationalization for chemistries that are well suited for superheated conditions (e.g., additions to carbonyl functions, aromatic substitutions, as well as C−Y [Y = N, O, S, C, Br, Cl] heterolytic cleavages). Lastly, we bring the reader to a rational decision analysis toward superheated flow conditions. We believe this Account will become a reference guide for exploring extended chemical spaces, accelerating organic synthesis, and advancing molecular sciences.

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Section: At Which Cost? Reactors Suitable For Superheated Flow Chemistrymentioning

confidence: 99%

New Opportunities for Organic Synthesis with Superheated Flow Chemistry

Bianchi,

Monbaliu

2024

Acc. Chem. Res.

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Enhancing electrochemical reactions in organic synthesis: the impact of flow chemistry

Regnier,

Vega,

Ioannou

et al. 2024

Chem. Soc. Rev.

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Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

Gasparetto,

Fődi,

Sipos

2024

Beilstein J. Org. Chem.

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Amino acids are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins, while also holding a crucial function in many biological processes. Due to their bifunctional character, they have been also used for combinatorial chemistry purposes, such as the preparation of DNA-encoded chemical libraries. We developed a practical synthesis for α-heteroaryl-α-amino acids starting from an array of small heteroaromatic halides. The reaction sequence utilizes a photochemically enhanced Negishi cross-coupling as a key step, followed by oximation and reduction. The prepared amino esters were validated for on-DNA reactivity via a reverse amidation–hydrolysis–reverse amidation protocol.

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Lab-scale flow chemistry? Just do it yourself!

Cited by 3 publications

References 153 publications

New Opportunities for Organic Synthesis with Superheated Flow Chemistry

New Opportunities for Organic Synthesis with Superheated Flow Chemistry

Enhancing electrochemical reactions in organic synthesis: the impact of flow chemistry

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

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